We have discovered two novel carbohydrate binding proteins, or lectins, in human endothelial cells, termed EL-1 and -2. Our long term goal is to understand the function of these lectins and how their biosynthesis and release are regulated. These lectins are quite similar in structure to a lectin we cloned from Xenopus oocyte cortical granules, XL35, which functions in the block to polyspermy. XL35 shows a monomer size of 45 kDa, forms putative decamers in solution, requires calcium to bind its oligosaccharide ligand, is a secreted, soluble protein, and displays no homology to lectins other than EL-1 and -2. EL-1 mRNA is expressed in a unique set of tissues: heart, small intestine, colon, thymus, lymph node, spleen, and a few others, but not in brain, kidney, or lung. By contrast, EL-2 mRNA is only expressed in small intestine. Immunohistological examination of a number of these tissues using antiserum against XL35 showed exclusive localization of EL-1 in blood vessel endothelia. Two cultured endothelial cells express EL-1 mRNA and protein that cross-reacts with anti-XL35 antibody: a transformed mouse lymph node endothelial cell line and a human aortic primary cell line. The chromosomal localization of both lectins is 1q23, the same locus at which the selectins are encoded, as well as other endothelial cell adhesion molecules. Our aims are: 1) To understand the mechanisms for the unique tissue expression patterns for EL-1 and -2, to describe the biosynthetic pathway and localization of EL-1 in cultured cells, and to determine the signals that cause the release of the lectins; 2) To determine the nature and structure of the glycoconjugate and oligosacchande ligand(s) for EL-1 and EL-2, how their expression is regulated, and the consequences of EL-glycoconjugate recognition and binding; 3) To determine if the mouse homologs of the lectins are expressed during embryogenesis and to investigate their function by constructing transgenic mice with homozygous deletions of the EL genes. Our hypothesis is that there is a signal, perhaps a cytokine or hormone, that causes the extracellular release of the stored EL, much as fertilization and calcium influx stimulates release of XL35 from the oocyte cortical granules. The released lectins can then recognize and bind their targets, perhaps on circulating cells, initiating adhesion, either among these target cells or between the target cells and endothelia or substrata. The structure of the lectins, their chromosomal localization, and presence in the secretory pathway of a cultured cell type suggest that they function in unique cell adhesion events mediated by endothelial cell present in an unusual set of tissues. Endothelia mediate many medically relevant adhesion events, including initial events in atherosclerosis, inflammation, and metastasis. Understanding the function of these novel lectins, therefore, may well have important medical applications.